Tie-Over Bolster Pressure Dressing Improves Outcomes of Skin Substitutes Xenografts on Athymic Mice

Abstract

The efficacy of skin substitutes is established for the treatment of burn injuries, but its use is not limited to this condition. This technology has the potential to improve the treatment of various conditions by offering highly advanced and personalized treatments. In vivo studies are challenging but essential to move to clinical use in humans. Mice are the most widely used species in preclinical studies, but the main drawback of this model is the limited surface area of the graft in long-term transplantation studies caused by the displacement and the contraction of the graft. We improved the conventional surgical procedures by stabilizing the chamber covering the graft with intramuscular sutures and by adding a tie-over bolster dressing. The current study was therefore performed to compare outcomes of skin grafts between the conventional and optimized skin graft model. Human self-assembled skin substitutes (SASSs) were prepared and grafted to athymic mice either by the conventional method or by the new grafting method. Graft healing and complications were assessed using digital photographs on postoperative days 7, 14, and 21. Similar structure and organization were observed by histological staining. The new grafting method reduced medium and large displacement events by 1.26-fold and medium and large contraction events by 1.8-fold, leading to a 1.6-fold increase in graft surface area compared to skin substitutes grafted with the usual method. This innovation ensures better reproducibility and consistency of skin substitute transplants on mice.

Production of Tissue-Engineered Skin Substitutes for Clinical Applications: Elimination of Serum

“…TES-4 samples were grafted onto the backs of CD1-Foxn1 nude mice (Charles River Laboratories, Wilmington, NC, USA), as previously described [ 32 , 33 ]. Briefly, a portion of the mid-back skin of the mouse was removed.…”

Cancer Spheroids Embedded in Tissue-Engineered Skin Substitutes: A New Method to Study Tumorigenicity In Vivo

“…Human keratinocytes and fibroblasts were isolated from the foreskin of a healthy individual (14 days old) as previously described [27]. Primary fibroblasts and HeLa cells (ATCC CCL-2) were cultured in fibroblast medium (Dulbecco-Vogt modified Eagle medium (Gibco™, Waltham, MA, USA) supplemented with 10% Avantor Seradigm FB Essence serum (Avantor ® , Radnor, PA, USA), 100 U/mL penicillin (Sigma-Aldrich, St. Louis, MO, USA) and 25 µg/mL gentamicin (Gemini Bio, West Sacramento, CA, USA)).…”

“…Tissue-engineered skin substitutes (TESs) were produced as previously described [27]. Briefly, fibroblasts were seeded at 4 × 10 3 cells/cm 2 onto an 85 cm 2 rectangular culturetreated dish.…”

“…Each cancerous skin substitute was grafted onto the back of a nude athymic mouse (Crl:CD1-Foxn1 n ; Charles River Laboratories, Laval, QC, Canada) within a Fusenig chamber, allowing to encase the skin substitute as previously described [27]. Briefly, a 2.5 × 2.5 cm square was cut out of the skin substitute.…”